Alternative titles; symbols
ORPHA: 90625; DO: 0111736;
Cytogenetic location: Xp21.2 Genomic coordinates (GRCh38): X:29,300,001-31,500,000
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| Xp21.2 | Deafness, X-linked 3 | 300030 | X-linked | 2 |
Lalwani et al. (1994) described a family with a nonsyndromic X-linked form of sensorineural hearing loss. The auditory impairment in affected males was congenital, bilateral, profound and sensorineural, affecting all frequencies and without evidence of radiographic abnormalities of the temporal bone. Adult carrier females manifested bilateral, mild to moderate high frequency sensorineural hearing impairment of delayed onset.
In the 3-generation family studied by Pfister et al. (1998), affected males were deaf at birth and female carriers had stable moderate hearing loss above 1 kHz. History and physical examinations revealed no stigmata of syndromic hearing loss. Funduscopic examination was normal.
Lalwani et al. (1994) described a family with a nonsyndromic X-linked form of sensorineural hearing loss mapping to Xp21.2. No recombination events were noted with markers within the Duchenne muscular dystrophy locus (DMD; 310200). There was, however, no clinical evidence of Duchenne or Becker muscular dystrophy (300376) in any family member.
One family with congenital sensorineural deafness with X-linked inheritance (304500), studied by Reardon et al. (1991), did not show linkage to Xq13-q21.1 and did not show the temporal bone changes of the gusher-deafness syndrome. Thus, this may represent the same entity as that in the family reported by Lalwani et al. (1994).
Pfister et al. (1998) identified a family in Turkey with deafness in which the disease mapped to the same region as DFN4. In contrast to the family reported by Lalwani et al. (1994), the crossover points were entirely within the DMD locus, suggesting that DFN4 is either an allele of DMD or a mutation in a DMD-nested gene. The restriction of the DFN4 locus to DMD suggested that dystrophin (300377) may play an important role in hearing.
There is evidence supporting the involvement of the dystrophin gene in hearing: the mdx mouse, which harbors a nonsense mutation in exon 23 of the Dmd gene, has been shown to have auditory dysfunction by auditory brainstem-response testing (Raynor and Mulroy, 1997). Mutations in 'unconventional' myosin-7 (MYO7A; 276903) have been demonstrated in Usher syndrome (hearing loss and retinitis pigmentosa), as well as in nonsyndromic deafness. Another structural gene, the human 'diaphanous' gene (DIAPH1; 602121), has been shown to be linked causally to the form of autosomal dominant deafness in the Monge family of Costa Rica (DFNA1; 124900).
Petersen et al. (2008) proposed the designation DFNX3 for this locus.
Lalwani, A. K., Brister, J. R., Fex, J., Grundfast, K. M., Pikus, A. T., Ploplis, B., San Agustin, T., Skarka, H., Wilcox, E. R. A new nonsyndromic X-linked sensorineural hearing impairment linked to Xp21.2. Am. J. Hum. Genet. 55: 685-694, 1994. [PubMed: 7942846]
Petersen, M. B., Wang, Q., Willems, P. J. Sex-linked deafness. Clin. Genet. 73: 14-23, 2008. [PubMed: 18005182] [Full Text: https://doi.org/10.1111/j.1399-0004.2007.00913.x]
Pfister, M. H. F., Apaydin, F., Turan, O., Bereketoglu, M., Bylgen, V., Braendle, U., Zenner, H. P., Lalwani, A. K. A second family with nonsyndromic sensorineural hearing loss linked to Xp21.2: refinement of the DFN4 locus within DMD. Genomics 53: 377-382, 1998. [PubMed: 9799605] [Full Text: https://doi.org/10.1006/geno.1998.5538]
Raynor, E. M., Mulroy, M. J. Sensorineural hearing loss in the mdx mouse: a model of Duchenne muscular dystrophy. Laryngoscope 107: 1053-1056, 1997. [PubMed: 9261007] [Full Text: https://doi.org/10.1097/00005537-199708000-00009]
Reardon, W., Middleton-Price, H. R., Sandkuijl, L., Phelps, P., Bellman, S., Luxon, L., Pembrey, M. E., Malcolm, S. A multipedigree linkage study of X-linked deafness: linkage to Xq13-q21 and evidence for genetic heterogeneity. Genomics 11: 885-894, 1991. [PubMed: 1783396] [Full Text: https://doi.org/10.1016/0888-7543(91)90011-3]